Effects of artemether on pancreatic islet morphology, islet cell turnover and α-cell transdifferentiation in insulin-deficient Glu;ROSA26-eYFP diabetic mice

Objectives: The antimalarial drug artemether is suggested to effect pancreatic islet cell transdifferentiation, presumably through activation γ-aminobutyric acid receptors, but this biological action is contested. Methods: We have investigated changes in α-cell lineage in response to 10-days treatment with artemether (100 mg/kg oral, once daily) on a background of β-cell stress induced by multiple low-dose streptozotocin (STZ) injection in GluCreERT2; ROSA26-eYFP transgenic mice. Key findings: Artemether intervention did not affect the actions of STZ on body weight, food and fluid intake or blood glucose. Circulating insulin and glucagon were reduced by STZ treatment, with a corresponding decline in pancreatic insulin content, which were not altered by artemether. The detrimental changes to pancreatic islet morphology induced by STZ were also evident in artemether-treated mice. Tracing of α-cell lineage, through co-staining for glucagon and yellow fluorescent protein (YFP), revealed a significant decrease of the proportion of glucagon+YFP- cells in STZ-diabetic mice, which was reversed by artemether. However, artemether had no effect on transdifferentiation of α-cells into β-cells and failed to augment the number of bi-hormonal, insulin+glucagon+, islet cells. Conclusions: Our observations confirm that artemisinin derivatives do not impart meaningful benefits on islet cell lineage transition events or pancreatic islet morphology.